National Cancer Institute

at the National Institutes of Health

Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®)

Health Professional Version

Treatment of Recurrent Childhood CNS Embryonal Tumors

Recurrence of all forms of central nervous system (CNS) embryonal tumors is not uncommon and usually occurs within 36 months of treatment. However, recurrent tumors may develop many years after initial treatment.[1,2] Disease may recur at the primary site or may be disseminated at the time of relapse. Sites of noncontiguous relapse may include the spinal leptomeninges, intracranial sites, and cerebrospinal fluid, in isolation or in any combination, and may be associated with primary tumor relapse.[1-3] Extraneural disease relapse may occur but is rare and is seen primarily in patients treated with radiation therapy alone.[4][Level of evidence: 3iiiA]

Studies have found that even in patients with nondisseminated disease at diagnosis, and independent of the dose of radiation therapy or the type of chemotherapy, approximately one-third of patients will relapse at the primary tumor site alone, one-third will relapse at the primary tumor site plus distant sites, and one-third will relapse at distant sites without relapse at the primary site.[1-3]

Treatment Options

There are no standard treatment options for recurrent childhood CNS embryonal tumors.

In most children, treatment is palliative and disease control is transient in patients previously treated with radiation therapy and chemotherapy, with over 90% progressing within 12 to 18 months. For young children, predominantly those younger than 3 years at diagnosis who were never treated with radiation therapy, longer-term control with reoperation, radiation therapy, and chemotherapy is possible.[3,5-7]

Surgery

At the time of relapse, a complete evaluation for extent of recurrence is indicated for all embryonal tumors. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities such as secondary tumors and treatment-related brain necrosis may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the lesion, and clinical symptomatology.

Radiation therapy

Patients with recurrent embryonal tumors who have already received radiation therapy and chemotherapy may be candidates for further radiation therapy depending on the site and dose of previous radiation, including reirradiation at the primary tumor site, focal areas of radiation therapy to sites of disseminated disease, and rarely, craniospinal radiation therapy. In most cases, such therapy is palliative. Stereotactic radiation therapy and/or salvage chemotherapy can also be used (see below).[8]

Chemotherapy

Recurrent CNS embryonal tumors can be responsive to chemotherapeutic agents used singularly or in combination, including cyclophosphamide, cisplatin, carboplatin, lomustine, etoposide, topotecan, and antiangiogenic metronomic therapy.[5,9-16]; [17,18][Level of evidence: 2A]

Approximately 30% to 50% of these patients will have objective responses to conventional chemotherapy, but long-term disease control is rare.

For select patients with recurrent medulloblastoma, primarily infants and young children who were treated at the time of diagnosis with chemotherapy alone and developed local recurrence, long-term disease control may be obtained after further treatment with chemotherapy plus local radiation therapy; this potential may be greatest in patients who are able to undergo complete resection of the recurrent disease.[19][Level of evidence: 2A]; [20][Level of evidence: 3iiiA]

With such regimens, objective response is frequent, occurring in 50% to 75% of patients; however, long-term disease control is obtained in less than 30% of patients and is primarily seen in patients in first relapse and in those with only localized disease at the time of relapse.[7]; [24][Level of evidence: 2A]; [25][Level of evidence: 3iiB]

Additionally, results from national trials for relapsed medulloblastoma that specified intent to transplant as part of their treatment plan showed that only approximately 5% of patients initiating retrieval therapy achieve long-term disease-free survival with this strategy.[24,28] Thus, studies that report from the time of transplant overestimate the benefit of transplant-based approaches for the total population of relapsing patients.